Some materials, when buried or implanted in bone defects, react with the bone and are directly chemically combined with the bone. These materials are called bioactive materials and are further classified into superficial bioactive materials, where the reaction occurs only on the surface of the materials; and bioresorbable materials, where the reaction occurs even inside the materials and the materials are gradually replaced with the bone. Exemplary commercialized superficial bioactive materials include hydroxyapatite ceramics (e.g., trade name APACERAM™ supplied by HOYA CORPORATION, Japan); and exemplary commercialized bioresorbable materials include beta phase tricalcium phosphate ceramics (e.g., trade name OSferion™ supplied by Olympus Terumo Biomaterials Corp., Japan).
Calcium carbonate (CaCO3) and gypsum (CaSO4H2O) are also known to be bioresorbable. These substances, however, have low strength and toughness and are difficult to be machined. In contrast, biodegradable polymers such as poly(lactic acid)s, poly(glycolic acid)s, copolymers of them, and polycaprolactones are highly flexible and are easy to be machined. The biodegradable polymers, however, do not show osteogenic ability (bone forming ability) because their biodegradability is derived from the phenomenon that they are degraded in vivo and are discharged therefrom. In addition, there have been some reports that some of the biodegradable polymers may affect surrounding tissues because they are degraded typically into lactic acid or glycolic acid upon degradation and thus show acidity. Under such circumstances, there have been made investigations to provide composite materials between these inorganic compounds and organic compounds to allow the composite materials to have both osteogenic ability and bioresorbability and further have improved mechanical properties. For example, Japanese Unexamined Patent Application Publication (JP-A) No. 2001-294673 discloses a process for the preparation of a bioresorbable material by combining a poly (lactic acid) and a calcium carbonate. Specifically, this document refers to a process for synthesizing a bioresorbable material by mixing a calcium carbonate containing vaterite as a principal component with a biodegradable polymer compound such as a poly (lactic acid), which vaterite is highly soluble in water among such calcium carbonates. This technique is also advantageous in that the pH is always maintained around neutrality, because even when the poly (lactic acid) is decomposed to be acidic, the acidity is neutralized by the buffering effects of the calcium carbonate as dissolved.
In this unprecedented aged society, bone defects should be desirably cured as soon as possible, because it is very important to maintain and ensure mastication and exercise performance for the health maintenance. To improve osteogenic ability, there have been attempted to incorporate, to a bioresorbable membrane, a factor such as a bone formation inducer (see Japanese Unexamined Patent Application Publication (JP-A) No. H06 (1994)-319794), or a proliferation factor or a bone morphogenic protein (see Japanese Unexamined Patent Application Publication (Translation of PCT Application) (JP-A) No. 2001-519210; and Japanese Unexamined Patent Application Publication (JP-A) No. 2006-187303). However, it is difficult to handle these factors. Accordingly, demands have been made to develop a bioresorbable material having superior bone reconstruction ability to allow the bone to self-regenerate more reliably and more rapidly.
In view of recent trends of researches and technologies for bio-related materials, the main stream of researches has been shifted from a materials design for the bonding of a material with the bone to a materials design for the regeneration of the bone; in these researches, the role of silicon in bone formation has received much attention; and a variety of silicon-doped materials have been designed (TSURU Kanji, OGAWA Tetsuro, and OGUSHI Hajime, “Recent Trends of Bioceramics Research, Technology and Standardization”, Ceramics Japan, 41, 549-553 (2006)). For example, there has been reported that the controlled release of silicon can act on cells to promote bone formation (H. Maeda, T. Kasuga, and L. L. Hench, “Preparation of Poly(L-lactic acid)-Polysiloxane-Calcium Carbonate Hybrid Membranes for Guided Bone Regeneration”, Biomaterials, 27, 1216-1222 (2006)). Independently, when composites of a poly(lactic acid) with one of three types of calcium carbonates (calcite, aragonite, and vaterite) are prepared and soaked in a simulated body fluid (SBF), the composite of the poly(lactic acid) with vaterite forms a hydroxyapatite having bone-like composition and dimensions within a shortest time among the three composites (H. Maeda, T. Kasuga, M. Nogami, and Y Ota, “Preparation of Calcium Carbonate Composite and Their Apatite-Forming Ability in Simulated Body Fluid”, J. Ceram. Soc. Japan, 112, S804-808 (2004)). These findings demonstrate that the use of vaterite, which can gradually release silicon, is believed to be a key to provide a material that produces more rapid bone reconstruction.
To use a material for filling bone defects, the affected area (bone defect) is incised and a dense or porous material, having such a size as to fill the affected area sufficiently, is directly implanted therein, or a granular material is charged into the affected area.
To ensure bone formation, it is desirable to implant or bury such a material in the affected area without a gap (clearance). However, it is not easy to process a dense or porous material so as to fit the dimensions of the affected area snuggly. In addition, a granular material, if charged into the affected area, often drops off from the affected area after the surgery (implantation). These techniques are therefore susceptible to improvements.
Independently, there is also known a guided bone regeneration technique that uses a masking membrane to cover a bone defect. The guided bone regeneration technique does not involve charging a material into the affected area. Instead, this techniques uses a masking membrane, which has the functions of preventing the invasion of cells and tissues not involved in bone formation into the bone defect, allowing the self-regeneration ability of the bone to exhibit, and helping the bone to reconstruct. This technique is intended to cure the bone defect by using the curing ability that a living body inherently has. For example, Japanese Unexamined Patent Application Publication (JP-A) No. 2009-61109 discloses a guided bone regeneration membrane and a production method thereof, wherein guided bone regeneration membrane has a bi-layer structure including a first nonwoven fabric layer and a second nonwoven fabric layer, in which the first nonwoven fabric layer contains a silicon-releasable calcium carbonate and a biodegradable resin as principal components, and the second nonwoven fabric layer contains a biodegradable resin as a principal component. It has been reported that the use of this membrane gives satisfactory proliferation of murine osteoblast-like cells (MC3T3-E1 cells), and when a bone defect formed in a rabbit cranial bone is covered by such a membrane, satisfactory bone formation (osteogenesis) is observed (see T. Wakita, A. Obata and T. Kasuga, “New Fabrication Process of Layered Membranes Based on Poly (Lactic Acid) Fibers for Guided Bone Regeneration”, Materials Transactions, 50 [7], 1737-1741 (2009)). This membrane, however, is not usable as a material for filling bone defects because it has a small thickness of from 230 to 300 μm. In addition, the bulk density of such membranes, estimated to be about 0.4 g/cm3 or more, is generally too high to be used as a material for filling bone defects.